Specific regulation of point-mutated K-ras-immortalized cell proliferation by a photodynamic antisense strategy

Maiko Higuchi, Asako Yamayoshi, Kiyoko Kato, Akio Kobori, Norio Wake, Akira Murakami

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14 Citations (Scopus)

Abstract

It has been reported that point mutations in genes are responsible for various cancers, and the selective regulation of gene expression is an important factor in developing new types of anticancer drugs. To develop effective drugs for the regulation of point-mutated genes, we focused on photoreactive antisense oligonucleotides. Previously, we reported that photoreactive oligonucleotides containing 2′-O-psoralenylmethoxyethyl adenosine (2′-Ps-eom) showed drastic photoreactivity in a strictly sequence-specific manner. Here, we demonstrated the specific gene regulatory effects of 2′-Ps-eom on [ 12Val]K-ras mutant (GGT GTT). Photo-cross-linking between target mRNAs and 2′-Ps-eom was sequence-specific, and the effect was UVA irradiation-dependent. Furthermore, 2′-Ps-eom was able to inhibit K-ras-immortalized cell proliferation (K12V) but not Vco cells that have the wild-type K-ras gene. These results suggest that the 2′-Ps-eom will be a powerful nucleic acid drug to inhibit the expression of disease-causing point mutation genes, and has great therapeutic potential in the treatment of cancer.

Original languageEnglish
Pages (from-to)37-43
Number of pages7
JournalOligonucleotides
Volume20
Issue number1
DOIs
Publication statusPublished - Feb 1 2010
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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